A physical examination that is relevant to the clinical situation should be performed. The pulse rate and blood pressure should be obtained, since a rapid pulse rate may suggest hyperthyroidism, and hypertension may occur in the context of multiple endocrine neoplasia, type II (MEN II). The neck should be carefully palpated for regional lymphadenopathy. While the presence of ipsilateral enlarged lymph nodes strongly suggests thyroid cancer, their absence in no way rules out malignancy. A smooth, soft, easily mobile nodule suggests benignancy, as does the presence of tenderness. Deviation of the trachea, which suggests a mass, should be noted. The thyroid gland should be carefully palpated, and the location, size, consistency, and mobility of the nodule(s) and the presence or absence of tenderness should be noted. A firm to hard, irregular, fixed, nontender nodule is more likely to be a thyroid malignant neoplasm, although some thyroid cancers are smooth and not particularly hard; conversely, some benign nodules can be very hard because of calcifications.

Multinodularity, especially if the nodules all have the same consistency, is consistent with a benign multinodular goiter. A nodule or mass that is dominant in size or has a different consistency than other nodules within the gland should be evaluated by employing the same criteria as those outlined for single nodules. A midline nodule over the hyoid bone that moves up with protrusion of the tongue is likely to be a thyroglossal duct cyst.